Streamlining Molecular Biology Through Automation

Recovery of high quality nucleic acid is a fundamental starting point for a multitude of molecular biology assays, including sequencing, cloning and PCR. Success of these assays hinges on sample quality and yield, and as such, practical considerations regarding the nucleic acid extraction process itself come into play.

There are many factors to bear in mind when selecting the most efficient nucleic acid extraction workflow, but generally speaking, these center on balancing cost versus performance. More specifically, duration of the complete process (including total hands-on time) is an important consideration along, with consistency, sensitivity, system footprint and compatibility of source material.

Traditionally, nucleic acid extraction has relied on manual approaches, but these are extremely time- and labor-intensive. From the hazards of phenol/chloroform methods, through to the newer kits based on filtration and solid-phase capture approaches, all still require much in the way of hands-on time. While this may be adequate for occasional use, for the typical molecular biology laboratory, nucleic acid extraction is a basis for the majority of work carried out each and every day. Automating these workflows is therefore highly beneficial when considering cost versus performance.

Nucleic acid research technologies are currently witnessing extraordinary advances, from single-cell analysis to high-throughput genomic studies. The process of nucleic acid extraction must also evolve, therefore effectively realizing the potential of these exciting downstream applications, and avoiding a bottleneck at the sample preparation phase.

The smart solution

Molecular biology laboratories face diverse challenges in their nucleic acid extraction workflows, which are mainly dictated by scale of operation. Smaller laboratories, such as those involved in clinical research and forensic disciplines, with a throughput of perhaps 1000 samples per day face bottlenecks in terms of human resources and hence sample processing time. At the other end of the spectrum, larger laboratories working on a single study such as the identification of crop biomarkers may have resources for high-speed sample processing but are challenged instead by the sheer number of samples they face, processing between 50,000 to 200,000 samples per day. Benefits afforded by automation differ for each sized laboratory, with smaller operations benefiting from reduced labor, and larger laboratories from increased throughput and simultaneous sample processing around the clock.

Speed and efficiency is vastly improved by automation, with kits able to process 24 or even 96 samples in parallel. Furthermore, multiple kits can be processed in succession to maximize throughput as well as valuable walkaway time. With this in mind, it is easy to see how automation can be a beneficial adaptation in all laboratories, essential for mid- to high-throughput sample turnarounds. Although it is possible for the efficiency of manual kits to be marginally improved by processing multiple samples simultaneously, this introduces another significant hazard in the form of cross-contamination. Again, this is a risk diminished by automation, and even more so in systems implementing non-contacting dispensing techniques in liquid handling processes. Moreover, utilizing non-contact dispensing eradicates the need for tips altogether, which also leads to long term cost savings in the consumables budget.

Instead of working through the repetitive steps of a manual nucleic acid extraction protocol, an automated system frees up the valuable time of laboratory staff, enabling them to apply their expertise in tasks such as data analysis and reporting. In addition, even the most accurate pipette operator is still human and likely to introduce a certain level of error into liquid handling processes, compromising accuracy. In contrast, the consistency of an automated system ensures perfectly reproducible sample handling throughput the whole nucleic acid extraction process.

During periods when the system is running unsupervised, to ensure peace of mind, feedback on system status is possible via email, text message or pager. Furthermore, automation also assists in auditing and quality control procedures, with details such as date, time and conditions automatically logged on the system and referenced to each barcode-identified sample.

Choosing the right fit

Automation can benefit all sizes of a molecular biology laboratory relying on nucleic acid extraction processes. These automated systems come in an array of formats to fit a range of scales and applications.

In the present day, agriculture is relying more and more on the tools of biotechnology for improved crop breeding. For example, PCR-based approaches may be employed for the identification of biomarkers conferring advantageous traits such as increased yield, salt resistance or other phenotypic characters suiting specific local conditions. Carefully governed breeding events will give rise to thousands of plants, and only one or two individuals may carry the required genotype. This proverbial “needle in a haystack” screening program necessitates a high sample turnaround in DNA extraction. Solutions for such high-throughput sample processing can either rely on a single larger system or multiple smaller systems.

High-capacity, larger, automated systems covering the whole workflow may either be purchased from a single supplier or integrated from instruments supplied via multiple sources, which presents potential difficulties for servicing agreements and compatibility. In the past, complete systems lacked flexibility in terms of applications and future upgrades, but a general trend the market is witnessing is a shift toward increased modularity and flexibility. For example, turnkey systems purchased from single vendors (such as the Thermo Fisher Scientific Automated Nucleic Acid Extraction WorkStation) provide comprehensive technical support and expertise, with the whole system in mind. The system will be covered by a single service contract, while optional swap-out programs ensure minimal downtime in the unlikely event of a breakdown. Workflow scheduling software is compatible across all instruments within the workflow, allowing simultaneous running of multiple processes.

As an alternative to a single larger system, running multiple smaller systems provides a failsafe approach, ensuring continuous processing in the event of instrument servicing or breakdown. Although covering a larger total footprint, this approach offers several additional benefits in terms of flexibility. Systems can be reconfigured, and individual instruments swapped in and out, as required. This also means the system is amenable to expansion in the future to meet the needs of an evolving laboratory, providing maximum flexibility depending on specific user requirements. These include expanded capacity with multiple plate hotels, increased throughput with multiple DNA extraction modules and covering other areas of the workflow such as lysate plate preparation (Figure 1).

Another discipline particularly benefiting from this multi-system approach is clinical research. Instead of one large and focused operation, as in crop biomarker identification, the dynamic needs of a clinical research department are likely to see lower throughputs in sample processing, but instead may encompass various projects.

Depending on the needs of downstream applications, there are multiple automated formats available to provide an effective solution to the challenges faced by a diverse range of molecular biology operations.

Overall goal

The goal of automation is to maximize workflow efficiency and throughput. Automated systems present the next step for mid- to high-throughput nucleic acid extraction workflows in almost any sized laboratory, ensuring high-speed sample processing without compromising sample yield and integrity. Ensuring consistency, accuracy and cost-efficiency, automation reduces hands-on processing time and increases sample throughput, guaranteeing a streamlined workflow.

Furthermore, we are now well into the “omics” era. Innovative high-throughput technologies, especially in the areas of genomics and transcriptomics, are continually advancing and becoming increasingly accessible to many research laboratories. The process of nucleic acid extraction must undergo similar adaptations in order to meet the needs of these downstream applications, facilitating the smooth running of nucleic acid extraction workflows in all molecular biology laboratories.